Repression of the vertebrate organizer by Wnt8 is mediated by Vent and Vox

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Abstract
Dorsoventral (DV) patterning of vertebrate embryos requires the concerted action of the Bone Morphogenetic Protein (BMP) and Wnt signaling pathways. In contrast to our understanding of the role of BMP in establishing ventral fates, our understanding of the role of Wnts in ventralizing embryos is less complete. Wnt8 is required for ventral patterning in both Xenopus and zebrafish; however, its mechanism of action remains unclear. We have used the zebrafish to address the requirement for Wnt8 in restricting the size of the dorsal organizer. Epistasis experiments suggest that Wnt8 achieves this restriction by regulating the early expression of the transcriptional repressors Vent and Vox. Our data show that vent and vox are direct transcriptional targets of Wnt8/β-catenin. Additionally, we show that Wnt8 and Bmp2b co-regulate vent and vox in a dynamic fashion. Thus, whereas both Wnt8 and zygotic BMP are ventralizing agents that regulate common target genes, their temporally different modes of action are necessary to pattern the embryo harmoniously along its DV axis.